由细胞外基质结构决定的肿瘤免疫逃逸和消除的独特进化模式。

IF 3.5 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Journal of The Royal Society Interface Pub Date : 2025-07-01 Epub Date: 2025-07-09 DOI:10.1098/rsif.2025.0116
Yijia Fan, Jason T George
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引用次数: 0

摘要

癌症进展仍然是一个重大的临床挑战。肿瘤细胞的表型适应导致疾病异质性,从而驱动治疗抵抗和免疫逃逸。t细胞免疫疗法虽然对某些癌症亚型有效,但也可能由于肿瘤免疫原性或t细胞识别的限制而失败。例如,免疫逃逸的一个潜在因素涉及肿瘤周围细胞外基质(ECM)的密度和排列,也称为肿瘤相关胶原蛋白特征(TACS)。然而,排列纤维导致患者存活率下降的具体机制尚未解耦。在这里,我们开发了EVO-ACT(基于进化试剂的癌症T细胞相互作用),这是一个基于二维代理的建模框架,旨在研究不同的TACS结构如何影响肿瘤进化和与CD8 T细胞的动态相互作用。我们的研究结果强调,tacs驱动的t细胞动力学调节,结合表型适应,如上皮细胞到间质细胞的转变,是肿瘤免疫原性差异的基础,我们的模型的应用可以成功地概括临床观察到的乳腺癌生存趋势。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Distinct evolutionary patterns of tumour-immune escape and elimination determined by extracellular matrix architectures.

Cancer progression remains a significant clinical challenge. Phenotypic adaptation by tumour cells results in disease heterogeneity, which drives treatment resistance and immune escape. T-cell immunotherapy, while effective at treating some cancer subtypes, can also fail due to limits on tumour immunogenicity or T-cell recognition. For example, one potential contributor to immune escape involves the density and alignment of the extracellular matrix (ECM) surrounding tumours, also known as tumour-associated collagen signature (TACS). However, the specific mechanisms by which aligned fibres contribute to decreased patient survival rates have not yet been decoupled. Here, we developed EVO-ACT (EVOlutionary agent-based cancer T-cell interaction), a two-dimensional agent-based modelling framework designed to investigate how different TACS architectures impact tumour evolution and dynamic interactions with CD8[Formula: see text] T cells. Our results highlight that TACS-driven modulation of T-cell dynamics, combined with phenotypic adaptation, such as epithelial-to-mesenchymal transition, underlies differences in tumour immunogenicity and the application of our model can successfully recapitulate clinically observed breast cancer survival trends.

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来源期刊
Journal of The Royal Society Interface
Journal of The Royal Society Interface 综合性期刊-综合性期刊
CiteScore
7.10
自引率
2.60%
发文量
234
审稿时长
2.5 months
期刊介绍: J. R. Soc. Interface welcomes articles of high quality research at the interface of the physical and life sciences. It provides a high-quality forum to publish rapidly and interact across this boundary in two main ways: J. R. Soc. Interface publishes research applying chemistry, engineering, materials science, mathematics and physics to the biological and medical sciences; it also highlights discoveries in the life sciences of relevance to the physical sciences. Both sides of the interface are considered equally and it is one of the only journals to cover this exciting new territory. J. R. Soc. Interface welcomes contributions on a diverse range of topics, including but not limited to; biocomplexity, bioengineering, bioinformatics, biomaterials, biomechanics, bionanoscience, biophysics, chemical biology, computer science (as applied to the life sciences), medical physics, synthetic biology, systems biology, theoretical biology and tissue engineering.
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